Respiratory syncytial virus (RSV) is the most common cause of serious lower respiratory illness in infants and young children worldwide. Immunoprotection is incomplete after a subject has been exposed to RSV such that repeat infections occur throughout life often with serious complications in the elderly and immune compromised patients. Unfortunately, while numerous vaccine candidates have been proposed and studied, there is no safe and effective vaccine available and treatment options are limited.
RSV displays two major surface viral proteins, the G (attachment) and the F (fusion) glycoproteins. The RSV F glycoprotein is much more effective in inducing protective immunity in animal model systems. Consequently, efforts to treat and prevent RSV infection have often focused on anti-RSV F protein antibodies, antiviral drugs that affect the F protein, and live virus or F protein-based vaccines. For example, prophylactic treatment with a palivizumab (a neutralizing, anti-RSV F protein monoclonal antibody) decreases the incidence of serious RSV induced infection in high-risk infants and young children. Palivizumab is not effective in treating active infection and as such is limited in its use. Similarly, other treatments for acute RSV infection also proved ineffective or minimally effective. For example, the antiviral Ribavirin has limited efficacy and is seldom used except for treatment of infection in immunocompromised patients. Without being limited to a single hypothesis, one possible explanation for the ineffectiveness of existing RSV treatments is that the virus-induced host inflammatory response is important to disease pathogenesis and this inflammatory response is only partially responsive to antiviral therapy once infection is established. Consequently, effective treatment may require both anti-inflammatory and antiviral components.
The G protein of RSV may play a role in inducing and modulating the host immune response to infection. Intact RSV G protein expression in the infecting virus is associated with a lower frequency of IFNγ expressing cells and a higher frequency of IL-4 expressing cells. RSV G protein has also been associated with increased pulmonary eosinophilia after RSV challenge in formalin-inactivated RSV vaccinated mice, increased pulmonary levels of substance P in RSV challenged mice, and decreased respiratory rates associated with its administration to mice.
Efforts to make a safe and effective vaccine have failed to date. One problem in developing a vaccine is the fact that a formalin inactivated vaccine led to more serious disease with later RSV infection when administered to young children, leading to concerns that any non-live RSV vaccine may be unsafe in young children. Another problem with prior art vaccines is an inability to induce a highly effective protective immune response. This problem is highlighted by the fact that natural infection provides only limited protection from reinfection and disease.
As such, there is a need for a safe and effective vaccine for RSV.